Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

BackgroundThe safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.MethodsSorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS).ResultsTwenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively.ConclusionsThis study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib.Trial RegistrationClinicalTrials.gov NCT00712790.背景 序贯放射性栓塞联合索拉非尼治疗的安全性与耐受性尚未明确。本研究为一项开放标签、单臂、研究者发起的Ⅱ期临床试验（临床试验编号：NCT0071279），在4个亚太地区中心开展，旨在评估序贯放射性栓塞联合索拉非尼治疗无法接受根治性治疗的肝细胞癌（hepatocellular carcinoma, HCC）患者的安全性与有效性。 方法 采用单次手术方式给予钇-90（yttrium-90, 90Y）树脂微球实施放射性栓塞，术后14天启动索拉非尼给药方案（400mg，每日两次）。本研究的主要终点为安全性、耐受性以及采用实体瘤疗效评价标准1.0版（RECIST v1.0）评估的最佳总体缓解率（overall response rate, ORR）。次要终点包括疾病控制率（完全缓解[CR]、部分缓解[PR]与疾病稳定[SD]之和）以及总生存期（overall survival, OS）。 结果 共纳入29例巴塞罗那临床肝癌（Barcelona Clinic Liver Cancer, BCLC）分期为B期（38%）或C期（62%）的肝细胞癌患者，患者接受的90Y微球中位给药剂量为3.0GBq（四分位距：1.0），随后接受索拉非尼治疗（中位日剂量：600.0mg；中位治疗时长：4.1个月）。28例患者出现至少1种不良反应，其中15例（52%）不良反应等级≥3级。最佳总体缓解率为25%，包含2例（7%）完全缓解、5例（18%）部分缓解以及15例（54%）疾病稳定。BCLC B期与C期患者的疾病控制率分别为100%与65%。2例（7%）患者因获得充分缓解而得以接受根治性治疗。BCLC B期与C期患者的中位生存期分别为20.3个月与8.6个月。 结论 本研究证实序贯放射性栓塞联合索拉非尼治疗具有潜在疗效，且不良反应可控可管理。 试验注册 临床试验注册号：NCT00712790（ClinicalTrials.gov）。